Mechanochemical Sensing of Single and Few Hg(II) Ions Using Polyvalent Principles.

Sensitivity of biosensors is set by the dissociation constant (Kd) between analytes and probes. Although potent amplification steps can be accommodated between analyte recognition and signal transduction in a sensor to improve the sensitivity 4-6 orders of magnitude below Kd, they compromise temporal resolution. Here, we demonstrated mechanochemical sensing that broke the Kd limit by 9 orders of magnitude for Hg detection without amplifications. Analogous to trawl fishing, we introduced multiple Hg binding units (thymine (T)-T pairs) in a molecular trawl made of two poly-T strands. Inspired by dipsticks to gauge content levels, mechanical information (force/extension) of a DNA hairpin dipstick was used to measure the single or few Hg2+ ions bound to the molecular trawl, which was levitated by two optically trapped particles. The multivalent binding and single-molecule sensitivity allowed us to detect unprecedented 1 fM Hg ions in 20 min in field samples treated by simple filtrations.